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Synthesis 2006(18): 3015-3018  
DOI: 10.1055/s-2006-942547
PAPER
© Georg Thieme Verlag Stuttgart · New York

A Stereoselective Anti-Aldol Route to (3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-ol: A Key Ligand for a New Generation of HIV Protease Inhibitors

Arun K. Ghosh*, Jianfeng Li, Ramu Sridhar Perali
Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, USA
Fax: +1(765)4961612; e-Mail: akghosh@purdue.edu;
Further Information

Publication History

Received 27 April 2006
Publication Date:
02 August 2006 (online)

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Abstract

A stereoselective synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol, an important high affinity P2-ligand, in high enantiomeric excess (>99%) is reported. The synthesis features an ester-derived titanium enolate based highly stereoselective anti-aldol reaction as the key step.

Key Words

antiviral agents - asymmetric synthesis - chiral auxiliary - aldol reactions - fused-ring systems

6

On June 23, 2006, the FDA approved a new HIV treatment for patients who do not respond to existing drugs; see: www.fda.gov/bbs/topics/NEWS/2006/NEW01395.html.

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The Mosher ester was formed by the reaction of Mosher acid and alcohol 3 with EDCI in the presence of DMAP. The 19F NMR analysis of the Mosher ester13 revealed an enantiomeric purity of >99%.